Platelets or thrombocytes in mammals are small, irregularly shaped cell-like compartments in blood without a nucleus, which are derived from precursor megakaryocytes. Platelets play a fundamental role in hemostasis. Platelets isolated from peripheral blood are an autologous source of growth factors. In the art various platelet concentrates have been used to accelerate soft-tissue and hard-tissue healing. Platelet concentrates are blood-derived products traditionally used for example to treat consequences of thrombopenia. It has long been recognized that several components in blood a part of the natural healing process and can accelerate healing when added to surgical sites
Fibrin glue is formed by polymerizing fibrinogen with thrombin and calcium. It was originally prepared using donor plasma; however, because of the low concentration of fibrinogen in plasma, the stability and quality of fibrin glue were low.
Platelet rich plasma (PRP) in a sense is an autologous modification of fibrin glue, which has been described and used in various applications with apparent clinical success. PRP obtained from autologous blood is used to deliver growth factors in high concentrations to the site of bone defect or a region requiring augmentation. Platelet-rich plasma (PRP) is an easily accessible source of growth factors to support bone- and soft-tissue healing. It is derived by methods that concentrate autologous platelets and is added to surgical wounds or grafts and to other injuries in need of supported or accelerated healing. A blood clot is the center focus of initiating any soft-tissue healing and bone regeneration. In all natural wounds, a blood clot forms and starts the healing process. PRP is a simple strategy to concentrate platelets or enrich natural blood clot, which forms in normal surgical wounds, to initiate a more rapid and complete healing process. A natural blood clot contains 95% red blood cells, 5% platelets, less than 1% white blood cells, and numerous amounts of fibrin strands. A PRP blood clot contains 4% red blood cells, 95% platelets, and 1% white blood cells.
While the use of PRP in bone healing does have a sound scientific basis, its application appears only beneficial when used in combination with osteoconductive scaffolds. Aggressive processing techniques and very high concentrations of PRP may not improve healing outcomes. Moreover, many other variables exist in PRP preparation and use that influence its efficacy; the effect of these variables should be understood when considering PRP as a therapeutic measure.
Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates allowing a simplified processing and handling. The slow polymerizing PRF membrane is particularly favorable to support the healing process, however, the biology behind the effect of PRF is still largely unknown and it is only suggested that the effect is due to certain soluble molecules are most likely trapped in fibrin meshes of PRF. PRF is also used in combination with freeze-dried bone allograft to enhance bone regeneration in sinus floor elevation.
Several techniques for platelet concentrates are available and their application may be confusing because each method leads to a different product with different biology and potential uses.
WO2010/089379A1 describes the combination of anticoagulated (soluble) platelet rich plasma (PRP) with a coagulation factor to activate PRP when administering the combination to a patient.
US2009/0047242A1 describes a conditioned blood composition which is prepared by incubating blood in a vessel that has a specific surface area to induce factors and cytokines, such as Interleukin-6.
WO2010/02047A1 describes a blood product comprising fibrin, thrombocytes and leukocytes, which is obtained by surface activation of blood coagulation.
WO2007/127834A2 discloses a thrombin composition obtained by contacting whole blood, a component thereof or fraction thereof with a contact activation agent, such thrombin composition containing a stabilizing agent, such as ethanol.
The terminology of these platelet concentrates, including PRP, PRF, platelet gel, fibrin glue and also platelet poor plasma (PPP) remains uncertain and their effect—despite the several positive results obtained in certain situations, controversial. A general classification is of these products is suggested by Dohan et al (Curr Pharm Biotechnol. 2012 June; 13(7):1131-7.).
Bone ischemia or ischemic bone necrosis (avascular necrosis, osteonecrosis, bone infarction, aseptic necrosis) is a disease wherein cellular death (necrosis) of bone components is due to an interruption of the blood supply of the bone tissue. As a result, the bone tissue dies; this necrosis of cell touches at the first place hematopoietic cells. If the disease affects the bones of a joint, it probably leads to destruction of the joint articular surfaces. Ischemic bone necrosis may be caused e.g. by traumatic injury, fracture or dislocation of the bones, dislocated hip or excessive alcohol consumption or use of steroids.
Upon reperfusion, repair of ischemic bone occurs. At first, mesenchymal cells and macrophages migrate from the living bone tissue grow into the dead bone marrow spaces and then the mesenchymal cells differentiate into osteoblasts and fibroblasts.
Possible treatment includes the replacement of the dead tissue and/or the use of compounds, which may reduce the rate of bone breakdown. There is still a need, however, for materials, which facilitate bone regeneration after the ischemic event.
Recent advances in regenerative medicine shed light on the capabilities of various growth factors, which have remarkable effects as inducers of bone formation. In addition to bone morphogenic proteins, platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-beta), insulin-like growth factor (IGF) and epidermal growth factor (EGF) also have a positive effect on bone regeneration. Single factor therapies are available as recombinant products, currently BMP-2, -7, and PDGF have marketing approval, or as natural extracts typically isolated from venous blood.
Positive effects of PRP in dental tissue repair and in other maxillofacial cases are widely practiced. PRP is also applied for the treatment of other pathologies such as osteoarthritis, tendinitis and nerve injury and is gaining traction as a ‘cure-all’ for many musculoskeletal diseases. However, the exact mode of action is unknown and the general perception of PRP is that both the protocols and the results are highly variable.